Linked Life Data

7905787

Source:http://linkedlifedata.com/resource/pubmed/id/7905787

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1994-3-14
pubmed:abstractText
The molecular basis of cross-resistance to tumor necrosis factor (TNF) and Adriamycin has been investigated using the breast adenocarcinoma cell line MCF7/p, its Adriamycin-resistant counterpart MCF7AdrR, and the MDR1 gene-transduced MCF-7 cells (MCF7/MDR1). While the parental cell line MCF7/p was TNF-sensitive, MCF7AdrR was TNF-resistant. The TNF resistance exhibited by MCF7AdrR cells was not due to a lack of TNF receptor expression because both cell lines express comparable levels of p75 and p55 receptors as revealed by immunofluorescence analysis. NF-kappa B translocation, which is an essential transducing signal of the TNF-induced lysis pathway, does not appear to be involved in this resistance as assessed by gel shift experiments. In order to determine the role of MDR1 gene expression in the development of this cross-resistance, MCF7/p cells transfected by the MDR1 gene were examined. Our data showed that the expression of the MDR1 gene in these cells resulted in a relative resistance of these cells to Adriamycin without affecting their susceptibility to TNF killing. The implication of the manganese superoxide dismutase and endogenous TNF expression in the cross-resistance by MCF7AdrR cells to Adriamycin and TNF has also been investigated. Northern blot analysis indicated that following TNF stimulation, the expression of 4-kilobase and 1-kilobase manganese superoxide dismutase mRNAs were 9- to 10-fold induced in MCF7AdrR cells as compared to MCF7/p and MCF7/MDR1 cells. This suggests a possible involvement of this enzyme in the Adriamycin-induced resistance to TNF. Although TNF-treatment of MCF7/p and MDR-cells induced endogenous TNF expression in these cells, the level of mRNA induction was selectively enhanced in MCF7AdrR cells (7- to 8-fold greater in MCF7AdrR cells as compared to MCF7/p and MCF7/MDR1 cells). Collectively, these data indicate that the expression of the MDR1 gene in MCF7/p cells following gene transfection is not sufficient for the acquisition of TNF resistance by MCF7/MDR1 cells. Furthermore, our data provide the first evidence that Adriamycin-induced resistance to TNF in MCF7AdrR cells may, in part, involve an overexpression of endogenous TNF and manganese superoxide dismutase genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
54
pubmed:geneSymbol
MnSOD, TNF
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
825-31
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7905787-Adenocarcinoma, pubmed-meshheading:7905787-Breast Neoplasms, pubmed-meshheading:7905787-Carrier Proteins, pubmed-meshheading:7905787-Down-Regulation, pubmed-meshheading:7905787-Doxorubicin, pubmed-meshheading:7905787-Drug Resistance, pubmed-meshheading:7905787-Drug Screening Assays, Antitumor, pubmed-meshheading:7905787-Enzyme Induction, pubmed-meshheading:7905787-Female, pubmed-meshheading:7905787-Gene Expression, pubmed-meshheading:7905787-Gene Expression Regulation, Enzymologic, pubmed-meshheading:7905787-Gene Expression Regulation, Neoplastic, pubmed-meshheading:7905787-Gene Transfer Techniques, pubmed-meshheading:7905787-Humans, pubmed-meshheading:7905787-Membrane Glycoproteins, pubmed-meshheading:7905787-P-Glycoprotein, pubmed-meshheading:7905787-RNA, Messenger, pubmed-meshheading:7905787-Receptors, Tumor Necrosis Factor, pubmed-meshheading:7905787-Signal Transduction, pubmed-meshheading:7905787-Superoxide Dismutase, pubmed-meshheading:7905787-Tumor Cells, Cultured, pubmed-meshheading:7905787-Tumor Necrosis Factor-alpha
pubmed:year
1994
pubmed:articleTitle
Resistance to TNF-alpha and adriamycin in the human breast cancer MCF-7 cell line: relationship to MDR1, MnSOD, and TNF gene expression.
pubmed:affiliation
Laboratory of Immunology, URA 1156 CNRS, Villejuif, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't